Bristol’s Opdivo shows huge promise in non-small cell lung cancer

One of the frontrunners in the new generation of immunotherapy treatments has shown huge promise in treating non-small cell lung cancer (NSCLC).

Bristol-Myers Squibb’s nivolumab (Opdivo) has already been approved for use in Japan against unresectable melanoma, but is now being assessed by regulators for use against squamous NSCLC, the biggest cancer killer of all.

Late last week the company released data from its phase 2, open label Checkmate -063 study, which showed the drug produced a one-year survival rate of 41 per cent in patients who had progressed after treatment with two prior therapies.

This result is a very significant improvement on the historical one-year survival rate for these patients, which is between 5.5 per cent and 18 per cent.

The trial’s main endpoint was the drug’s objective response rate, which was found to be 15% in patients treated with single agent Opdivo, and median duration of response was not reached.

Median overall survival was 8.2 months in the trial, which involved 117 patients. The median duration of response had not yet been reached.

Overall, the data suggest the drug could be a major advance, and could extend the lives of patients with NSCLC, but this will only be confirmed in Phase 3 trials.

The presentation of the data at the Chicago Multidisciplinary Symposium on Thoracic Oncology sent BMS’s share price soaring, rising more than 8 per cent on the news.

Nivolumab is one of the frontrunners in a new generation of PD-1/PD-L1 checkpoint inhibitors which reveal the tumour to the body’s immune system, allowing it to attack the cancer.

Merck’s rival Keytruda (pembrolizumab) is the only other PD-1/PD-L1 approved in the US so far, approved for advanced melanoma. Keytruda has just been granted Breakthrough Therapy Designation for NSCLC but BMS is in pole position in the disease.  Lung cancer is by far the biggest cancer market, and claims the lives of around 1.5 million people each year according to the World Health Organization, and NSCLC accounts for approximately 85 percent of these cases.

BMS will use the data as part of its ‘rolling submission’ of data to the FDA and EMA, and now looks on course to gain approval for NSCLC in 2015.

Sanford Bernstein analyst Tim Anderson forecasts sales of the drug could reach $4.6 billion by 2020, the final figure depending on how many indications the drug can win in that time.

The drug did produce some significant side-effects in patients, although these were expected in patients with advanced disease. Fatigue, lung tissue inflammation and diarrhoea were among the most common adverse side effects reported.

The discontinuation rate due to drug-related side effects was 12 percent, and there were two drug-related deaths in patients with multiple co-morbidities and in the setting of progressive disease.

“The Phase 2 findings from CheckMate -063 are encouraging as there are no effective treatment options for patients with refractory squamous cell lung cancer after their disease has progressed through two prior therapies,” said Suresh S. Ramalingam, MD, Professor and Director of Medical Oncology, Winship Cancer Institute of Emory University. “The results are also consistent with Phase 1 data previously reported from Study -003.”

Nivolumab is being investigated in four Phase 3 trials as a single agent – three in previously treated patients (CheckMate -017, CheckMate -057 and CheckMate -153 ) and one in chemotherapy-naïve patients (CheckMate -026). The company’s other immunotherapy is Yervoy, and this is being investigated in two Phase 3 trials in combination with chemotherapy in newly diagnosed small cell lung cancer (Study -156) and squamous cell NSCLC (Study -104).

The FDA is due to rule on BMS’ first submission of the drug, for advanced melanoma, by 30 March 2015, with an EMA decision expected around the same time.

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